The gut microbiome regulates host glucose homeostasis via peripheral serotonin

Alyce M Martin; Julian M Yabut; Jocelyn M Choo; Amanda J Page; Emily W Sun; Claire F Jessup; Steve L Wesselingh; Waliul I Khan; Geraint B Rogers; Gregory R Steinberg; Damien J Keating

doi:10.1073/pnas.1909311116

The gut microbiome regulates host glucose homeostasis via peripheral serotonin

Proc Natl Acad Sci U S A. 2019 Oct 1;116(40):19802-19804. doi: 10.1073/pnas.1909311116. Epub 2019 Sep 16.

Authors

Alyce M Martin¹, Julian M Yabut^{2

3}, Jocelyn M Choo^{1

4}, Amanda J Page^{5

6}, Emily W Sun¹, Claire F Jessup¹, Steve L Wesselingh^{1

4}, Waliul I Khan^{3

7

8}, Geraint B Rogers^{1

4}, Gregory R Steinberg^{9

3

10}, Damien J Keating^{11

5}

Affiliations

¹ Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, SA 5042, Australia.
² Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada.
³ Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON L8S 4K1, Canada.
⁴ Microbiome & Host Health, South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia.
⁵ Nutrition & Metabolism, South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia.
⁶ Centre for Nutrition and Gastrointestinal Disease, Adelaide Medical School, University of Adelaide, Adelaide, SA 5000, Australia.
⁷ Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON L8S 4K1, Canada.
⁸ Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada.
⁹ Division of Endocrinology and Metabolism, Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada; [email protected] [email protected].
¹⁰ Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada.
¹¹ Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, SA 5042, Australia; [email protected] [email protected].

Abstract

The gut microbiome is an established regulator of aspects of host metabolism, such as glucose handling. Despite the known impacts of the gut microbiota on host glucose homeostasis, the underlying mechanisms are unknown. The gut microbiome is also a potent mediator of gut-derived serotonin synthesis, and this peripheral source of serotonin is itself a regulator of glucose homeostasis. Here, we determined whether the gut microbiome influences glucose homeostasis through effects on gut-derived serotonin. Using both pharmacological inhibition and genetic deletion of gut-derived serotonin synthesis, we find that the improvements in host glucose handling caused by antibiotic-induced changes in microbiota composition are dependent on the synthesis of peripheral serotonin.

Keywords: glucose homeostasis; microbe−host interactions; microbiome; serotonin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Bacterial Agents / pharmacology
Area Under Curve
Blood Glucose / metabolism
Gastrointestinal Microbiome*
Gene Deletion
Glucose / metabolism*
Glucose Tolerance Test
Homeostasis*
Male
Mice
Mice, Inbred C57BL
Random Allocation
Serotonin / physiology*

Substances

Anti-Bacterial Agents
Blood Glucose
Serotonin
Glucose

Grants and funding

201709FDN-CEBA-116200 /CIHR/Canada